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Males are from BDNF, females are from…

By Timothy Cocks Science and the world 07 Jul 2015

Reported in Nature Neuroscience last week

Sex divide seen in mechanism that produces persistent pain

“Research showing that male and female mice regulate pain sensitivity differently raises questions about gender balance in experimental design.

The immune system has important roles in chronic pain, with cells called microglia being key players. Microglia express a protein called brain-derived neurotrophic factor (BDNF) to signal to spinal-cord neurons. When injury or inflammation occurs, this signal sensitizes the body to pain*, so that even light touch hurts

This confirmed that in males, hypersensitivity to pain depends on BDNF signals from microglia, but that in females it is mediated by some other mechanism.

Importantly, his team’s results may explain why some microglia-targeting pain drugs have failed in human clinical trials. “Maybe they failed because the biology is only true for half the population.”


Brought to mind some other work undertaken on sex differences and pain by Lauren Nicotra (who presented her work at the first PainAdelaide in 2013) and Mark Hutchinson:

Women experience more chronic pain than men – now we know why

“Over many years, pain researchers have firmly established that women do experience more pain than men. Unfortunately, the majority of chronic pain conditions predominately affect the female sex.

The search for these elusive mechanisms that contribute to the sex differences in pain led us to look at the “other brain”, the immune like cells of the brain and spinal cord, termed glia. Glia are a collection of immune-like cells that outnumber neurons ten to one** throughout the brain and spinal cord.

Female sex hormones oestrogen and progesterone interact with the brain’s immune cells. The predominant female sex hormone, oestrogen has long been known to influence female pain. But new studies investigating pain across the female menstrual cycle have shown increased pain sensitivity when oestrogen levels peak in the cycle. (For a comprehensive review of this work, here is an open access paper)

Our research team has identified that the cellular and molecular generators of pain*** are fundamentally different between males and females. Critically, glia appear to be central to this sex difference in pain. Female pain is fundamentally different to male pain owing to the different reliance on glia.

I’ve always found this last statement to be interesting – “Female pain is fundamentally different to male pain owing to the different reliance on glia”. The neuroimmune substrate of pain clearly has differences between males and females in some instances, but does this make pain itself – the experience of pain, fundamentally different? That’s probably a Pinot Noir question.


-Tim Cocks


* Not happy with this wording

** This is controversial and most likely wrong

*** Don’t like this wording either


  1. Nice one Tim,
    The male and female construction of the pain experience maybe different but how can one judge or measure the intensity of that experience, and the impact of that experience on any one individual, male or female. That has to remain very subjective personal and, sometimes very private.

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